Human papillomaviruses (HPV) target epithelial tissues for infection and are etiological agents of a variety of cancers, predominantly squamous cell carcinomas and adenocarcinomas. HPV-associated cancers include those of the head and neck (larynx, oral cavity, oropharynx, tonsils, and esophagus), respiratory tissue, breast, skin, cervix, and anus. Although HPV infection is considered a necessary factor in development of some cancers, other factors may also affect carcinogenesis (Braakhuis et al., 2004, J. Natl. Cancer Inst. 96(13): 998-1006; Dahlstrand et al., 2004, Anticancer Res. 24(3b): 1829-35; Daling et al., 2004, Cancer 101 (2): 270-80; Ha et al., 2004, Crit. Rev. Oral Biol. Med. 15(4): 188-96; Hafkamp et al., Acta Otolaryngol 124(4): 520-6; Harwood et al., 2004, Br. J. Dermatol. 150(5):949-57; Rees et al., 2004, Clin. Otolaryngol 29(4):301-6; Widschwendter et al., 2004, J. Clin. Virol. 31 (4):292-7).
At least 77 different types of HPV have been identified. Of those, HPV16 and HPV18 are frequently linked to a variety of HPV-associated cancers, but the risk level associated with a HPV type may vary with different forms of papilloma-associated cancers. The pathogenesis of human papillomaviruses in epithelia has been studied to elucidate the link of HPV infection to cancers. HPV infect basal layer cells of stratified epithelia where they become established as multicopy episomes or integrated genomes, by which the viral DNA is replicated with cellular chromosomes (reviewed by Longworth et al., 2004, Microbiol. Mol. Biol. Rev. 68(2):362-72). At cell division, a daughter cell migrates away from the basal layer and undergoes differentiation in which HPV vegetative viral replication and late-gene expression are activated to produce progeny HPV. Although an infected individual's immune system may clear the HPV infection, usually within 1 to 2 years, infected basal cells may persist for decades. HPV infection may lead to chromosomal instability and aneupolidy that may favor HPV integration (Melsheimer et al., 2004, Clin. Cancer Res. 10(9):3059-63; Reidy et al., 2004, Laryngoscope 114(11): 1906-9). During HPV genome integration, the HPV E2 gene may be destroyed, resulting in deregulated expression of the HPV E6/E7 oncogenes that encode oncoproteins that target the regulatory proteins pRb and p53. Thus, a cascade of events that modulate cellular regulation may result in carcinogenesis (Braun et al., 2004, Cancer Lett. 209(1):37-49; Fan et al., 2004, Crit. Rev. Eukaryot. Gene Expr. 14(3):183-202; Fiedler et al., 2004, FASEB J. 18(10):1120-2; Psyrri et al., 2004, Cancer Res., 64(9):3079-86; Si et al., 2004, J. Clin. Virol. 32(1):19-23).
The association of HPV infection and cervical cancer has been the subject of considerable research and epidemiological study because of the high incidence of cervical cancer worldwide, estimated at 450,000 new cases per year. HPV types associated with a high risk of developing cervical cancer (HR-HPV) include HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 73, although the epidemiological significance of individual types may vary with different geographical regions or clinical testing parameters (Munoz et al., 2004, Int. J Cancer 111(2): 278-85; Chaturvedi et al., 2005, J. Med. Virol. 75(1):105-13; Smith et al., 2004, Int. J. Gynaecol. Obstet. 87(2):131-7). HPV infections that are generally considered a low risk for developing into cervical cancer (LR-HPV) include HPV types 6, 11, 43, 44, 61, 71, and 72.
In women infected with HPV, cervical infection may lead to condylomata (genital warts), cervical intraepithelial neoplasia (CIN), and cervical cancer (Kahn et al., 2004, Adolesc. Med. Clin. 15(2): 301-21, ix). Cytological examination of cervical cells has been the primary screening tool for detecting cervical cancer in many countries, usually using the CIN grading system (1 to 3) to monitor precancerous lesions for determining treatment and/or further monitoring. In addition to cytological screening, molecular screening for HPV nucleic acid may be a cost-effective prognostic test that may allow extending the time interval between cytological tests (Wiley et al., 2004, Curr. Oncol Rep. 6(6): 497-506; Zielinski et al., 2004, Obstet. Gynecol. Surv. 59(7): 543-53; Glavel et al., 2004, Br. J. Cancer 90(9):1803-8). Molecular assays have been developed for detection of selected HPV proteins and nucleic acid sequences in human biological specimens, e.g., Pap smears and biopsies (Chen et al., 2005, Gynecol Oncol. 99(3):578-84; Carozzi et al., 2005, Am. J. Clin. Pathol. 124(5): 716-21; Molden et al., 2005, Cancer Epidemiol. Biomarkers Prev. 14(2): 367-72; Asato et al., 2004, J. Infect. Dis. 189(1):1829-32; Federschneider et al., 2004, Am. J. Obstet. Gynecol. 191(3): 757-61; Remmerbach et al., J. Clin. Virol. 30(4):302-8).
Vaccination against common HPV types may be useful to treat or prevent genital warts, condylomata, or prevent development of cancers, particularly cervical cancers. Various forms of HPV vaccinations are in development or testing (Ault et al., 2004, Vaccine 22(23-24):3004-7; Corona Gutierrez et al., 2004, Hum. Genet. Ther. 15(5):421-31; Harper et al., 2004, Lancet 364(9447):1757-65; Roden et al., 2004, Hum. Pathol. 35(8):971-82).
There is a need to efficiently and sensitively detect the presence of HPV in biological specimens to provide diagnostic and prognostic information to physicians treating patients infected with HPV, particularly for women whose cervical tissue has been infected with HR-HPV types. There is also a need to efficiently and sensitively detect the presence of HPV in biological specimens obtained from individuals who have been vaccinated against HPV infection, to determine the short-term and long-term efficacy of the vaccination.